The long-term goals of this proposed research are to further the understanding of the mmchanisms of cell-mediated immunity to tumors. Our emphasis will be on the analysis of the mechanisms of nonspecific cytotoxicity for tumor by normal macrophages activated by lymphocyte mediators. These are soluble factors elaborated by lymphocytes stimulated by antigen or mitogens, and are thought to play an important role in the amplification of the immune reaction initiated by contact of a small number of sensitized lymphocytes with specific antigen. The specific goals of the proposed work are: 1) Further characterization of the lymphocyte mediator, macrophage activating factor (MAF), which activates macrophages to kill tumor cells. 2) Further investigation on the role of simple carbohydrates in the interaction of MAF and macrophages leading to activation as assessed by cytotoxicity of tumor cells. 3) Studies to determine whether MAF activation of macrophages to kill tumor cells can be further enhanced by plasma esterase inhibitors. 4) Further investigation on the mechanism by which macrophages, once activated, kill tumor cells. Studies will emphasize problems of cell-to-cell contacts and the production of toxic soluble materials.